JPH0573728B2 - - Google Patents
Info
- Publication number
- JPH0573728B2 JPH0573728B2 JP87116632A JP11663287A JPH0573728B2 JP H0573728 B2 JPH0573728 B2 JP H0573728B2 JP 87116632 A JP87116632 A JP 87116632A JP 11663287 A JP11663287 A JP 11663287A JP H0573728 B2 JPH0573728 B2 JP H0573728B2
- Authority
- JP
- Japan
- Prior art keywords
- arteriosclerosis
- effect
- compound
- chloro
- cis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 17
- 208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 17
- 239000004480 active ingredient Substances 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- JQNJUZUDWVHVHJ-UHFFFAOYSA-N 8-chloro-1,5-benzothiazepine Chemical class N1=CC=CSC2=CC(Cl)=CC=C21 JQNJUZUDWVHVHJ-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 abstract description 32
- 239000000203 mixture Substances 0.000 abstract description 6
- 230000000069 prophylactic effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 description 19
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 18
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 16
- 229960001123 epoprostenol Drugs 0.000 description 16
- 238000012360 testing method Methods 0.000 description 14
- 241000283973 Oryctolagus cuniculus Species 0.000 description 10
- 235000012000 cholesterol Nutrition 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 230000003902 lesion Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000008719 thickening Effects 0.000 description 6
- 201000003371 Monckeberg arteriosclerosis Diseases 0.000 description 5
- 208000034189 Sclerosis Diseases 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 235000009200 high fat diet Nutrition 0.000 description 5
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 5
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 210000004231 tunica media Anatomy 0.000 description 4
- FTUXVMVEKYLKGE-WECFPGDBSA-N (z)-but-2-enedioic acid;[(2s,3s)-8-chloro-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate Chemical compound OC(=O)\C=C/C(O)=O.C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=C(Cl)C=C2S1 FTUXVMVEKYLKGE-WECFPGDBSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 210000000702 aorta abdominal Anatomy 0.000 description 3
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 3
- -1 cholesteryl ester Chemical class 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940099112 cornstarch Drugs 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229960001375 lactose Drugs 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 235000021590 normal diet Nutrition 0.000 description 3
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 230000003449 preventive effect Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- KFGOFTHODYBSGM-IJCBKZNRSA-N 6-Keto-prostaglandin F1a Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC(=O)CCCCC(O)=O KFGOFTHODYBSGM-IJCBKZNRSA-N 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 210000002376 aorta thoracic Anatomy 0.000 description 2
- 210000002565 arteriole Anatomy 0.000 description 2
- 230000003143 atherosclerotic effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 210000004026 tunica intima Anatomy 0.000 description 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- MBWVBOWYTCRZKR-BTJKTKAUSA-N 5H-1,2-benzothiazepin-4-one (Z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.S1N=CC(=O)CC2=CC=CC=C21 MBWVBOWYTCRZKR-BTJKTKAUSA-N 0.000 description 1
- BVABFIZTUSTDDW-UHFFFAOYSA-N 5h-1,2-benzothiazepin-4-one Chemical compound S1N=CC(=O)CC2=CC=CC=C21 BVABFIZTUSTDDW-UHFFFAOYSA-N 0.000 description 1
- WYWKPNIAGOEYTD-UHFFFAOYSA-N 8-chloro-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound N1C(=O)CCSC2=CC(Cl)=CC=C21 WYWKPNIAGOEYTD-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010065558 Aortic arteriosclerosis Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010072810 Vascular wall hypertrophy Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 201000001962 aortic atherosclerosis Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000036523 atherogenesis Effects 0.000 description 1
- 230000036778 atheroma formation Effects 0.000 description 1
- 210000001841 basilar artery Anatomy 0.000 description 1
- VTMPYKRCBKYPJR-UHFFFAOYSA-N benzoyl 4-hydroxybenzoate Chemical compound C1=CC(O)=CC=C1C(=O)OC(=O)C1=CC=CC=C1 VTMPYKRCBKYPJR-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000364 effect on atherosclerosis Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000010514 hydrogenated cottonseed oil Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003815 prostacyclins Chemical class 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002784 sclerotic effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical compound O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 229950000329 thiouracil Drugs 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11992886 | 1986-05-23 | ||
| JP61-119928 | 1986-05-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63107925A JPS63107925A (ja) | 1988-05-12 |
| JPH0573728B2 true JPH0573728B2 (es) | 1993-10-15 |
Family
ID=14773638
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62116632A Granted JPS63107925A (ja) | 1986-05-23 | 1987-05-12 | 動脈硬化症予防・治療剤 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4786634A (es) |
| EP (1) | EP0250814B1 (es) |
| JP (1) | JPS63107925A (es) |
| AT (2) | ATE79259T1 (es) |
| DE (1) | DE3781044T2 (es) |
| DK (1) | DK263787A (es) |
| FR (1) | FR2598914B1 (es) |
| GB (1) | GB2190587B (es) |
| HK (1) | HK62292A (es) |
| SG (1) | SG60092G (es) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4018018A1 (de) * | 1990-06-05 | 1991-12-12 | Schindler Wolfgang | Cd-plattengeraet |
| JP2658783B2 (ja) * | 1992-12-10 | 1997-09-30 | 田辺製薬株式会社 | 抗動脈硬化剤 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59157021A (ja) * | 1983-02-25 | 1984-09-06 | Tanabe Seiyaku Co Ltd | 動脈硬化症予防治療剤 |
| GB8315364D0 (en) * | 1983-06-03 | 1983-07-06 | Tanabe Seiyaku Co | 8-chloro-1 5-benzothiazepine derivatives |
| US4567175A (en) * | 1983-06-03 | 1986-01-28 | Tanabe Seiyaku Co., Ltd. | 8-Chloro-1,5-benzothiazepine derivatives |
| JPS59231018A (ja) * | 1983-06-10 | 1984-12-25 | Tanabe Seiyaku Co Ltd | 抗脂血剤 |
| US4585768A (en) * | 1984-04-10 | 1986-04-29 | Tanabe Seiyaku Co., Ltd. | 1,5-benzothiazepine derivatives and processes for preparing the same |
| JPS60258118A (ja) * | 1984-06-06 | 1985-12-20 | Kowa Co | 抗動脈硬化剤 |
| US4778791A (en) * | 1986-05-16 | 1988-10-18 | Tanabe Seiyaku Co., Ltd. | Pharmaceutical composition for improving constitution of lipids in blood |
-
1987
- 1987-05-12 US US07/049,169 patent/US4786634A/en not_active Expired - Fee Related
- 1987-05-12 JP JP62116632A patent/JPS63107925A/ja active Granted
- 1987-05-15 EP EP87107081A patent/EP0250814B1/en not_active Expired - Lifetime
- 1987-05-15 AT AT87107081T patent/ATE79259T1/de not_active IP Right Cessation
- 1987-05-15 DE DE8787107081T patent/DE3781044T2/de not_active Expired - Fee Related
- 1987-05-19 GB GB8711752A patent/GB2190587B/en not_active Expired - Fee Related
- 1987-05-22 DK DK263787A patent/DK263787A/da not_active Application Discontinuation
- 1987-05-22 FR FR878707258A patent/FR2598914B1/fr not_active Expired - Fee Related
- 1987-10-08 AT AT0262787A patent/AT390880B/de not_active IP Right Cessation
-
1992
- 1992-06-05 SG SG60092A patent/SG60092G/en unknown
- 1992-08-20 HK HK622/92A patent/HK62292A/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HK62292A (en) | 1992-08-28 |
| DK263787D0 (da) | 1987-05-22 |
| ATE79259T1 (de) | 1992-08-15 |
| EP0250814A3 (en) | 1990-01-31 |
| AT390880B (de) | 1990-07-10 |
| FR2598914A1 (fr) | 1987-11-27 |
| JPS63107925A (ja) | 1988-05-12 |
| EP0250814B1 (en) | 1992-08-12 |
| DE3781044D1 (de) | 1992-09-17 |
| FR2598914B1 (fr) | 1991-10-25 |
| EP0250814A2 (en) | 1988-01-07 |
| GB2190587A (en) | 1987-11-25 |
| GB8711752D0 (en) | 1987-06-24 |
| SG60092G (en) | 1992-09-04 |
| DE3781044T2 (de) | 1993-01-28 |
| GB2190587B (en) | 1990-01-17 |
| US4786634A (en) | 1988-11-22 |
| DK263787A (da) | 1987-11-24 |
| ATA262787A (de) | 1990-01-15 |
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